CA2450661A1 - Preparation of flumethasone and its 17-carboxyl androsten analogue - Google Patents

Preparation of flumethasone and its 17-carboxyl androsten analogue Download PDF

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Publication number
CA2450661A1
CA2450661A1 CA002450661A CA2450661A CA2450661A1 CA 2450661 A1 CA2450661 A1 CA 2450661A1 CA 002450661 A CA002450661 A CA 002450661A CA 2450661 A CA2450661 A CA 2450661A CA 2450661 A1 CA2450661 A1 CA 2450661A1
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CA
Canada
Prior art keywords
flumethasone
compound
formula
alpha
reacting
Prior art date
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Granted
Application number
CA002450661A
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French (fr)
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CA2450661C (en
Inventor
Ivan Villax
Zita Mendes
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HOVIONE Ltd
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Individual
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=20086054&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2450661(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Individual filed Critical Individual
Publication of CA2450661A1 publication Critical patent/CA2450661A1/en
Application granted granted Critical
Publication of CA2450661C publication Critical patent/CA2450661C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
    • C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
    • C07J5/0061—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16
    • C07J5/0069—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group
    • C07J5/0076—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group by an alkyl group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J3/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom
    • C07J3/005—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom the carbon atom being part of a carboxylic function
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • C07J71/0005—Oxygen-containing hetero ring
    • C07J71/001—Oxiranes
    • C07J71/0015—Oxiranes at position 9(11)
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pain & Pain Management (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Rheumatology (AREA)
  • Veterinary Medicine (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Control Of Combustion (AREA)
  • Reduction Or Emphasis Of Bandwidth Of Signals (AREA)
  • Oscillators With Electromechanical Resonators (AREA)
  • Anti-Oxidant Or Stabilizer Compositions (AREA)

Abstract

Process for preparing flumethasone (6.alpha.,9.alpha.-difluoro-11(3,17.alpha.,21-trihydroxy-16.alpha.-methyl-pregna-1,4-diene-3,20-dione), flumethasone 21-acetate or its 17-carboxyl androsten analogue of the formula:

which process comprises (a) reacting a compound of formula (II) with benzoyl chloride to form a 3-enolic ester of the formula (IIIa):

b) reacting the enol benzoate (IIIa) with an electrophilic fluorination agent to introduce fluorine in the C6- position to form a compound of formula (IIIb):

(c) deprotecting the compound (IIIb) at C3 to form a compound of formula (IV):
CA002450661A 2001-06-12 2002-06-11 Preparation of flumethasone and its 17-carboxyl androsten analogue Expired - Fee Related CA2450661C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
PT102628A PT102628B (en) 2001-06-12 2001-06-12 NEW PROCESS OF PREPARATION OF FLUMETHANONE AND ITS 17-CARBOXYL ANDROSTENE ANALOGUE
PT102.628 2001-06-12
PCT/GB2002/002644 WO2002100878A1 (en) 2001-06-12 2002-06-11 Preparation of flumethasone and its 17-carboxyl androsten analogue

Publications (2)

Publication Number Publication Date
CA2450661A1 true CA2450661A1 (en) 2002-12-19
CA2450661C CA2450661C (en) 2008-01-08

Family

ID=20086054

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002450661A Expired - Fee Related CA2450661C (en) 2001-06-12 2002-06-11 Preparation of flumethasone and its 17-carboxyl androsten analogue

Country Status (19)

Country Link
US (1) US6528666B1 (en)
EP (1) EP1395603B1 (en)
JP (1) JP4095018B2 (en)
CN (1) CN1244593C (en)
AT (1) ATE460422T1 (en)
AU (1) AU2002310616B2 (en)
CA (1) CA2450661C (en)
CY (1) CY1109960T1 (en)
DE (1) DE60235625D1 (en)
DK (1) DK1395603T3 (en)
ES (1) ES2338768T3 (en)
IL (2) IL159343A0 (en)
NO (1) NO326153B1 (en)
NZ (1) NZ530536A (en)
PL (1) PL206731B1 (en)
PT (1) PT102628B (en)
RU (1) RU2260596C1 (en)
WO (1) WO2002100878A1 (en)
ZA (1) ZA200309656B (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2473471A1 (en) * 2001-11-29 2003-06-12 Taro Pharmaceuticals U.S.A., Inc. Method for the preparation of 6-alpha-fluoro corticosteroids
ATE318274T1 (en) * 2002-12-09 2006-03-15 Sicor Inc PROCESS FOR PRODUCING 6 ALPA-FLUORINATED PREGNANS
EP1526139A1 (en) * 2003-10-24 2005-04-27 S.N.I.F.F. Italia S.P.A. A process for preparing highly pure androstane 17-beta-carboxylic acids and androstane 17-beta-carbothioic acid fluoromethyl esters
CN100429221C (en) * 2005-10-31 2008-10-29 浙江仙琚制药股份有限公司 Synthesis method of cortin
CN101759761B (en) * 2008-11-28 2012-08-08 天津金耀集团有限公司 Method for preparing steroid compounds containing 6alpha-F
US20120178124A1 (en) 2009-01-07 2012-07-12 Mitsubishi Chemical Corporation Sterol side chain-cleaving enzyme protein and use thereof
CN101942002A (en) * 2010-09-24 2011-01-12 岳阳环宇药业有限公司 Refining technology for steroid 21-position ester
ITMI20122200A1 (en) 2012-12-20 2014-06-21 Trifarma Spa PROCESS FOR THE PREPARATION OF 6-ALPHA-FLUORO PREGNANI
RU2532902C1 (en) * 2013-07-12 2014-11-20 Российская Федерация, от имени которой выступает Министерство промышленности и торговли Российской Федерации (Минпромторг России) Method of obtaining 11beta, 17 alpha, 21-trihydroxy-16alpha-methyl-9alpha-fluoropregna-1,4-diene-3,20-dione (dexamethazone) from phytosterol

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3499016A (en) 1958-08-04 1970-03-03 Upjohn Co 6alpha-fluoro-16alpha-methyl derivatives of the pregnane series
US3636010A (en) 1968-12-23 1972-01-18 Ciba Geigy Corp Esters of steroid-17-carboxylic acids
NL187577C (en) * 1978-04-05 1991-11-18 Sibla Srl 3-ACETOXY-9BETA, 11BETA-EPOXY-PREGNA-1,3,5-TRIEN, PROCESS FOR THE PREPARATION THEREOF, AND PROCESS FOR THE PREPARATION OF 6-alpha-halogen-1,4-diene-3-ones.
US4188322A (en) * 1978-04-28 1980-02-12 Blasinachim S.P.A. Process for the preparation of 6-halo-pregnanes
FR2701262B1 (en) 1993-02-05 1995-03-24 Roussel Uclaf New process for the preparation of 6 alpa, 9 alpha-difluorinated steroids and new intermediates.
IT1319663B1 (en) * 2000-11-17 2003-10-23 Farmabios Srl PROCESS FOR THE PREPARATION OF FLUORO-STEROIDS.

Also Published As

Publication number Publication date
NO326153B1 (en) 2008-10-06
NO20035517D0 (en) 2003-12-11
ES2338768T3 (en) 2010-05-12
CN1531544A (en) 2004-09-22
IL159343A0 (en) 2004-06-01
EP1395603A1 (en) 2004-03-10
PL367843A1 (en) 2005-03-07
DE60235625D1 (en) 2010-04-22
JP2004534795A (en) 2004-11-18
RU2260596C1 (en) 2005-09-20
EP1395603B1 (en) 2010-03-10
JP4095018B2 (en) 2008-06-04
IL159343A (en) 2010-11-30
ATE460422T1 (en) 2010-03-15
US6528666B1 (en) 2003-03-04
CN1244593C (en) 2006-03-08
AU2002310616A2 (en) 2002-12-23
PL206731B1 (en) 2010-09-30
PT102628B (en) 2010-09-09
DK1395603T3 (en) 2010-05-10
PT102628A (en) 2002-12-31
CY1109960T1 (en) 2014-09-10
WO2002100878A1 (en) 2002-12-19
NZ530536A (en) 2005-05-27
RU2004100309A (en) 2005-07-10
ZA200309656B (en) 2004-06-22
AU2002310616B2 (en) 2007-08-30
CA2450661C (en) 2008-01-08

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Legal Events

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EEER Examination request
MKLA Lapsed

Effective date: 20220301

MKLA Lapsed

Effective date: 20200831